Institute of Pharmacology, National Yang Ming University, 155, Sec. 2, Li-Nong Street, Taipei, 11217, Taiwan.
Faculty of Medicine, National Yang Ming University, Taipei 11221, Taiwan., 155, Sec. 2, Li-Nong Street, Taipei, 11221, Taiwan.
Mol Nutr Food Res. 2021 Feb;65(3):e2000937. doi: 10.1002/mnfr.202000937. Epub 2020 Dec 10.
Pathological bacterial translocation from the disrupted intestinal barrier leads to substantial complications and mortality in liver cirrhosis. Vitamin D is reported as beneficial to gut barriers in some animal models. However, its effect on cirrhotic bacterial translocation is unknown. The authors aim to investigate the effects of calcitriol on bacterial translocation in cirrhotic rats.
Cirrhotic rats are administrated with a 2-week course of active vitamin D (calcitriol, 0.1 μg kg per day) or vehicle by oral gavage after thioacetamide (TAA) injection for 16 weeks. Bacterial translocation, gut permeability, gut microbiota, and associated mechanisms are investigated. Calcitriol treatment significantly attenuates bacterial translocation and reduces intestinal permeability in TAA-induced cirrhotic rats. It upregulates the expressions of occludin in the small intestine and claudin-1 in the colon of cirrhotic rats directly independent of intrahepatic status. Even when a short period of calcitriol treatment do not reduce intestinal bacterial overgrowth, it induces a remarkable change of bacterial diversities and enrichment of Muribaculaceae, Bacteroidales, Allobaculum, Anaerovorax, and Ruminococcaceae.
Calcitriol treatment attenuates intestinal permeability, reduces bacterial translocation, and enriches potentially beneficial gut microbiota in cirrhotic rats that may enable it as a potential therapeutic agent to prevent cirrhotic complications.
从受损的肠道屏障中发生的病理性细菌易位会导致肝硬化患者出现严重并发症和死亡。有报道称，维生素 D 在某些动物模型中对肠道屏障有益。然而，其对肝硬化细菌易位的影响尚不清楚。作者旨在研究骨化三醇对肝硬化大鼠细菌易位的影响。
在硫代乙酰胺（TAA）注射 16 周后，给予肝硬化大鼠为期 2 周的活性维生素 D（骨化三醇，每天 0.1μg/kg）或载体口服灌胃。研究细菌易位、肠道通透性、肠道微生物群及相关机制。骨化三醇治疗可显著减轻 TAA 诱导的肝硬化大鼠的细菌易位并降低肠道通透性。它直接在不依赖于肝内状态的情况下上调肝硬化大鼠小肠中的紧密连接蛋白（occludin）和结肠中的 claudin-1 的表达。即使骨化三醇治疗的时间很短不能减少肠道细菌过度生长，它也会引起细菌多样性的显著变化，并富集 Muribaculaceae、拟杆菌目、Allobaculum、Anaerovorax 和 Ruminococcaceae。
骨化三醇治疗可减轻肝硬化大鼠的肠道通透性，减少细菌易位，并丰富潜在有益的肠道微生物群，这可能使其成为预防肝硬化并发症的潜在治疗剂。
